The biggest problem in the world today is antimicrobial resistance, which undermines human health and increases morbidity and mortality associated with life-threatening serious diseases. Scientists from different fields are therefore examining plants for their antimicrobial use in the face of multidrug-resistant bacteria with a new eye. So, the aim of this research to find a new antibacterial from five aqueous extracts of Nigella sativa, Ziziphus spina-christi, Rosmarinus officinalis, Origanum majorana, and Allium sativum medicinal plants tested against the most multidrug-resistant bacterial isolates from clinical specimens which were Klebsiella pneumoniae (Gram-negative), Escherichia coli (Gram-negative), Pseudomonas aeruginosa (Gram-negative), Staphylococcus aureus (Gram-positive) and Methicillin-resistant Staphylococcus aureus (Gram-positive). Also, to investigate the antibiofilm activity of the most potent extract. From all tested plants, the total extract of Z. spina-christi appeared a strong antibacterial effect against all tested MDR-strains. Besides, its polyphenol fraction showed a stronger effect. Furthermore, the total extract MIC ranged between 3.125-12.5 mg/ml with MBC was 3.125-25 mg/ml against previous strains. While, polyphenol fraction MIC and MBC were about 0.312-1.25 mg/ml and 0.312-2.5 mg/ml, respectively. In contrast to the antibacterial strength of polyphenol fraction, the antibiofilm effect was weaker than the total extract antibiofilm effect, where at ½ MIC, the reduction of biofilm was about 78.18%, 81.9% and 99.48% against S. aureus, MRSA and P. aeruginosa, respectively. While, in the case of polyphenol fraction, the biofilm reduction effect against previous strains was 63.82%, 59.97%, and 87.95%, respectively.